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Effect of apoptosis of CD4+ CD25+ regulatory T cells on proliferation as well as secretion of effector T cells and interventional activity of Xuebijing injection in septic rats.

Yu-hang AI ; Yong-ming YAO ; Xin-gui DAI

Chinese Journal of Surgery.2009;47(1):58-61.

OBJECTIVETo investigate the effect of apoptosis of CD4+ CD25+ regulatory T cells (Tregs) on proliferation as well as secretory function of effector T cells (Teff) and potential influence of Xuebijing injection on them in septic rats.

METHODSA sepsis model was reproduced by cecal ligation puncture (CLP), and Wistar rats were randomly divided into the control group (n = 8), sham-operated group (n = 8), CLP group (n = 8), and Xuebijing injection treatment group (n = 8). CD4+ CD25+ Tregs in each group were separated by immunomagnetic beads isolate system on day 3, the apoptosis rate, expression of forkhead/winged helix transcription factor p3 (Foxp3) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) on Tregs were analyzed by flow cytometry, and secretion levels of interleukin (IL)-10 from Tregs were measured by ELISA. Following co-culture of CD4+ CD25+ Treg with CD4+ CD25- T cells (1:1) for 68 hours, proliferative activity of Teff was determined by MTT, and IL-2/sIL-2R alpha levels were measured by ELISA.

RESULTSThe apoptosis rate of Tregs in control group was 12.03% +/- 0.89%, which was not significantly different from sham-operated group 9.48% +/- 2.17%. The apoptosis rate of Tregs in CLP group 5.87% +/- 0.44% was lower than that in control group (P < 0.01), and treatment with Xuebijing injection markedly enhanced the apoptosis of Tregs 27.29% +/- 2.48%. Compared to CLP group, expression of Foxp3, CTLA-4, and the secretion of IL-10 of Treg were significantly lowered in Xuebijing injection group (all P < 0.01). The Teff proliferative activity in response to ConA, and IL-2 levels of Teff in CLP group were significantly suppressed compared with control group (P < 0.01), and secretion of sIL-2R alpha in the supernatants was much higher than that of the control group. In comparison to the CLP group, inhibitory rate of Teff proliferative activity and the sIL-2R alpha levels were significantly decreased, while the secretion of IL-2 was increased in Xuebijing injection group (P <0.01).

CONCLUSIONCD4+ CD25+ Tregs could markedly upregulate the suppressive function on Teff in sepsis, and treatment with Xuebijing injection effectively enhanced apoptosis of Tregs, thereby down-regulating the suppression on Teff.

Animals ; Apoptosis ; Cell Proliferation ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Male ; Rats ; Rats, Wistar ; Sepsis ; drug therapy ; immunology ; T-Lymphocytes ; immunology ; pathology ; T-Lymphocytes, Regulatory ; immunology ; pathology

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Stimulating effect of sera from severe trauma patients on NF-kappaB activity in macrophage and its relationship with patients prognosis.

Hua-ping LIANG ; Xiang XU ; Hao XIA ; Jun FEI ; Dan WU ; Zheng-guo WANG

Chinese Journal of Surgery.2009;47(1):54-57.

OBJECTIVETo investigate the stimulating effect of sera from severe multiple trauma patients within 24 h post trauma on nuclear factor-kappaB (NF-kappaB) activity in macrophage and their relationship with patients prognosis.

METHODSPeripheral blood of 47 patients with multiple traumas with injury severity score (ISS) > or = 16 and 24 healthy volunteers were obtained, and sera samples were isolated. And 24 h after transfection of the recombinant NF-kappaB plasmid containing luciferase reporter gene into the mouse macrophage line (RAW 264.7), the cells were stimulated by sera from different patients for 6 h, then stimulating effect of sera on NF-kappaB was assessed by luciferase activity. The concentrations of interleukin-1 beta, tumor necrosis factor alpha, interleukin-10, interleukin-1 receptor antagonist, and soluble tumor necrosis factor receptor I were detected with ELISA kits.

RESULTSThe stimulating activity of sera from trauma patients on NF-kappaB was increased significantly, and it was higher in MODS group, non-survivor group than that in non-MODS, survivor group respectively. The level of activity was correlated positively with APACHE II score, while it did not have relationship to the cytokine or endogenous antagonist levels. The area under the receiver operating characteristic curve (ROC) of NF-kappaB activity for predicting MODS and mortality was significantly higher than that of APACHE II score.

CONCLUSIONEarly measurement of NF-kappaB stimulating activity of sera from severe multiple trauma patients may have the value to predict occurrence of MODS and mortality.

Adolescent ; Adult ; Animals ; Cell Line ; Female ; Humans ; Macrophages ; metabolism ; Male ; Mice ; Middle Aged ; Multiple Organ Failure ; blood ; pathology ; Multiple Trauma ; blood ; NF-kappa B ; metabolism ; Prognosis ; Serum ; Young Adult

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Expression of soluble human triggering receptors on myeloid cell-1 in patients with multiple trauma and its clinical significance.

Zhan-fei LI ; Xiang-jun BAI

Chinese Journal of Surgery.2009;47(1):51-53.

OBJECTIVETo investigate the expression profile of human soluble triggering receptor on myeloid cell-1 (sTREM-1) in patients with multiple trauma and determine its clinical significance.

METHODSPeripheral blood of 52 patients admitted to the hospital from October 2007 to January 2008 with multiple traumas with injury severity score (ISS) > or = 16 and 7 healthy volunteers were obtained, and sera samples were isolated. sTREM-1 was determined by semi-quantitative immunoblot technique. TNF-alpha and C-reactive protein (CRP) were determined by ELISA.

RESULTSsTREM-1 of patients with multiple traumas was significantly increased as compared with that of control (P < 0.001), and sTREM-1 of ISS > or = 25 group was significantly higher than that of 16 < or = ISS < 25 group (P < 0.05). sTREM-1 level correlated closely with TNF-alpha level (r = 0.845, P < 0.05), but did not correlate with CRP (r = 0.426, P > 0.05). In patients with sepsis, sTREM-1 on 1, 2 and 7 d was (25.1 +/- 2.2), (31.9 +/- 2.6) and (25.2 +/- 1.9) ng/L, respectively. In patients without sepsis, sTREM-1 on 1, 2 and 7 d was (15.8 +/- 1.3), (24.2 +/- 2.0) and (13.9 +/- 1.5) ng/L, respectively. sTREM-1 of patients with sepsis was significantly higher than that of patients without sepsis (P < 0.05).

CONCLUSIONSSerum sTREM-1 correlates closely with ISS, TNF-alpha and onset of sepsis, indicating that it may play an important role in the development of sepsis in patients with multiple traumas.

Adolescent ; Adult ; C-Reactive Protein ; metabolism ; Female ; Humans ; Male ; Membrane Glycoproteins ; blood ; Middle Aged ; Multiple Trauma ; blood ; complications ; immunology ; Myeloid Cells ; metabolism ; Receptors, Immunologic ; blood ; Sepsis ; etiology ; Triggering Receptor Expressed on Myeloid Cells-1 ; Tumor Necrosis Factor-alpha ; blood ; Young Adult

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Comparison of three different organ failure assessment score systems in predicting outcome of severe sepsis.

Xiao-pan LUO ; Hai-hong WANG ; Shuang-fei HU ; Shui-jing WU ; Guo-hao XIE ; Bao-li CHENG ; Chen ZHOU ; Xiang-ming FANG

Chinese Journal of Surgery.2009;47(1):48-50.

OBJECTIVETo compare multiple organ dysfunction score (MODS), the sequential organ failure assessment (SOFA) and the logistic organ dysfunction score (LODS) in predicting hospital mortality in severe sepsis.

METHODSFour hundred and three patients admitted to the ICU from December 2004 to November 2007 with a diagnosis of severe sepsis were enrolled in this study. Their MODS, SOFA, LODS and Acute Physiology and Chronic Health Evaluation (APACHE) II at admission and the highest score during hospitalization were respectively recorded and collected in regard to mortality. The discrimination of three multiple organ dysfunction score systems were assessed by the areas under the receiver operating characteristic curves (AUC).

RESULTSThe AUC of admission scores was 0.811 for LODS, 0.787 for SOFA, 0.725 for MODS, and 0.770 for APACHE II in predicting hospital mortality. All maximum scores had better power of discrimination than the admission scores (P < 0.01). The power of discrimination of LODS and SOFA were better than the MODS, either the admission or the highest, respectively (P < 0.01). However, no significant difference was observed between the LODS and the SOFA regarding mortality prediction (P > 0.05). The AUC value for the APACHE II score was much lower compared to LODS (P < 0.01). However, there was no difference in AUC value among APACHE II, SOFA and MODS (P > 0.05).

CONCLUSIONLODS, SOFA and MODS show a good discrimination power, while maximum LODS is of the highest discrimination power to predict the outcome of patient with severe sepsis.

APACHE ; Adult ; Aged ; Aged, 80 and over ; Female ; Hospital Mortality ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Multiple Organ Failure ; pathology ; Prognosis ; Sepsis ; mortality ; Severity of Illness Index

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Epidemiological study of severe sepsis in a newborn intensive care unit.

Zheng CHEN ; Bao-li CHENG ; Chun-xiao WANG ; Xiao-ying CHENG ; Li-ping SHI ; Xiang-ming FANG ; Li-zhong DU ; Qiang SHU

Chinese Journal of Surgery.2009;47(1):44-47.

OBJECTIVESTo determine the incidence and outcome of severe sepsis in Newborn Intensive Care Unit (NICU) and to characterize their demographics and infection pattern.

METHODSCharacteristics of 243 newborns admitted to NICU from June 1st, 2006 to May 31st, 2007 were retrospectively analyzed.

RESULTSAnalysis of data derived from 243 newborns admitted to NICU over an 1-year period with 48 (19.8%) cases diagnosed as severe sepsis, and 70.8% of them were males. The median age of severe sepsis patients was 2 (1-6 ) days. In 56.3% of the patients bacteria were isolated, and E. coli was the predominant microbe. PRISM score and mortality rate were higher in those with severe sepsis, while their Apgar score was lower than other cases. The overall hospital mortality of severe sepsis was 45.8%. Risk factors for hospital mortality included higher PRISM score, severe organ dysfunction, circulatory system dysfunction, and hematological or central nervous system dysfunction.

CONCLUSIONSThis study shows that severe sepsis is a common, frequently fatal morbid condition in critical ill newborns in NICU, showing similar disease pattern with other investigations. Further multiple-center investigations are helpful to prevent, control and salvage critically ill children suffering from severe sepsis.

Female ; Humans ; Incidence ; Infant, Newborn ; Intensive Care Units, Neonatal ; Male ; Retrospective Studies ; Sepsis ; epidemiology

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A clinical study on the diagnostic criteria of multiple organ dysfunction syndrome.

Chao WANG ; Qiang SU ; Shu-wen ZHANG ; Cheng-hong YIN ; Hong WANG ; Bao-en WANG

Chinese Journal of Surgery.2009;47(1):40-43.

OBJECTIVETo develop diagnostic criteria of multiple organ dysfunction syndrome (MODS) by a prospective and multi-center clinical investigation.

METHODSThe data of 1087 MODS cases obtained from ICU of 37 hospitals from March 2002 to January 2005 in 11 provinces in China were analyzed in order to derive the diagnostic criteria of MODS.

RESULTSThis MODS diagnostic criteria involved 7 organs. To diagnose MODS, the original cause of MODS should be identified, then there should be two or more organs showing signs of dysfunction. The criteria for organ dysfunction were as follows. (1) Cardiovascular system: SBP < 90 mm Hg (1 mm Hg = 0.133 kPa), MAP < 70 mm Hg, signs of shock, ventricular tachycardia, ventricular fibrillation, or myocardial infarction; (2) Respiratory system: oxygenation index < 300 mm Hg; (3) Nervous system: indifference, restlessness, lethargy, light coma, or deep coma, Glasgow score < or = 14; (4) Blood system: PLT < 100 x 10(9)/L; CT, APTT, and PT prolonged or shortened; positive plasma protamine paracoagulation; (5) Liver: TBIL > 20. 5 micromol/L, ALB < 28 g/L; (6) Kidney: Cr > 123.8 micromol/L, urinary volume < 500 ml/24 h; (7) Gastro-intestine: bowel sounds decreased or disappeared; retention in the stomach, or positive occult blood feces with dark stools or haematemesis; intraabdominal pressure (intravesical pressure) > or = 11 cm H2O (1 cm H2O = 0.098 kPa). Any organ function met with one of the above conditions was considered to have dysfunction.

CONCLUSIONSThis diagnostic criterion of multiple organ dysfunction syndrome has been developed by this research, but it needs to accumulate experience by clinical practice and to revise the diagnosis criteria.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Multiple Organ Failure ; diagnosis ; Prospective Studies ; Young Adult